The goal of the experiments outlined in this proposal is to characterize remote gene delivery to the spinal cored and brainstem of the superoxide dismutase (SOD1) mouse, an animal model of ALS, using adeno- associated virus. We will utilize viral vectors whose gene products are marker proteins, either beta-galactosidase or green fluorescent protein (GFP). After peripheral injection of vector into either the mouse sciatic nerve or brachial plexus, we will examine the corresponding CNS gene expression. We expect remote delivery of recombinant genes to the CNS through peripheral nervous system (PNS) injection to offer a number of potential advantages over direct CNS injections, including minimally invasive delivery of viral vectors with the potential for repeated treatments and a reduced inflammatory response. We hope to quantify gross GFP and beta-glactosidase expression in this study as well as discover biases in terms of which CNS cell types express these proteins. We also hope to confirm that retrograde axonal transport, not diffusion, is responsible for spinal cord expression. We will do this by blocking microtubule function with peripheral colchicine injection and also by analyzing beta-galactosidase distribution after injecting the protein peripherally. Our final aims involve observing the effects of remote virus delivery on neuronal cell viability and determining whether later reinjection and also be analyzing beta-galactosidase distribution after injecting the protein peripherally. Our final aim involve observing the effects of remote virus delivery on neuronal cell viability and determining whether later reinjection of vector enhances viral gene expression. Data from this study will aid in elucidating the rational choice of viral vector(s) and mode(s) of delivery for optimal expression of therapeutic proteins in the central nervous system of the ALS mouse model.